As2O3饮水慢性中毒对大鼠肝脏TRβ1介导的甲状腺激素信号通路的影响
Effects of chronic poisoning by As2O3 in drinking water on TRβ1-mediated thyroid hormone signaling pathway in rat liver
王炼 1王雪飞 2高魁 3郭迎春 3张天阳 4杨英5
作者信息
- 1. 河南牧业经济学院动物医药学院,河南郑州 450000;内蒙古农业大学兽医学院,内蒙古呼和浩特 010018
- 2. 河南牧业经济学院动物医药学院,河南郑州 450000
- 3. 鄂尔多斯市东胜区动物疫病预防控制中心,内蒙古鄂尔多斯 017000
- 4. 巴彦淖尔杭锦后旗农牧和科技局,内蒙古巴彦淖尔 015400
- 5. 内蒙古农业大学兽医学院,内蒙古呼和浩特 010018
- 折叠
摘要
As2O3能干扰大鼠血清甲状腺激素(TH)水平,引发慢性肝损伤,然而其机制仍不清楚.为了探明TH信号通路在As2O3引发慢性肝损伤中的作用,采用qRT-PCR、Western blot技术检测大鼠肝脏TH信号通路的关键调控因子TRβ1、核内途径TRβ1的下游因子(Cyclin D1)基因和蛋白表达变化,核外途经关键因子(Bax、Bcl-2)蛋白的变化.结果显示:与对照组相比,As2O3作用110 d,雌鼠肝脏TRβ1蛋白表达均显著降低(P＜0.01),0.1、0.2 mg/L组Cyclin D1表达显著升高(P＜0.01);雄鼠0.4 mg/L组TRβ1蛋白表达显著降低(P＜0.01),各组Cyclin D1的表达均显著升高(P＜0.01),mRNA表达结果与蛋白基本一致.与对照组相比,As2O3作用194 d,各组TRβ1蛋白表达显著降低(P＜0.01),Cyclin D1的表达均显著升高(P＜0.01),mRNA表达结果与蛋白基本一致.与对照组相比,As2O3干扰了大鼠Bcl-2和Bax蛋白表达,并随着作用时间的增长,诱导Bcl-2/Bax蛋白比值升高.其中,各组雌鼠和0.4 mg/L组雄鼠Bcl-2/Bax比值显著升高(P＜0.01),0.1 mg/L组雄鼠明显升高(P＜0.05).表明大鼠长期慢性饮水摄入As2O3会引起其肝脏TRβ1的基因和蛋白水平异常下降,Cyclin D1的水平异常升高,诱导Bcl-2/Bax蛋白比值升高.
Abstract
Previous studies have found that As2 O3 can interfere with serum thyroid hormone TH levels in rats and cause chronic liver damage,but the mechanism remains unclear.In order to ex-plore the role of TH signaling pathway in As2 O3-induced chronic liver injury,qRT-PCR and West-ern blot techniques were used to detect the expression changes of genes and protein of TRβ1(a key regulator of TH signaling pathway in rat liver)and cyclin D1(the downstream factor of TRβ1 in nuclear pathway).Meanwhile,the changes in the protein of key factors(Bax,Bcl-2)of the TH sig-nal nuclear outside pathway were detected.The results indicated that:after As2 O3 treatment for 110 days,compared with the control group,the expression of TRβ1 protein in the liver of female mice significantly decreased(P＜0.01),the expression of cyclin D1 significantly increased in the 0.1 and 0.2 mg/L groups(P＜0.01).Meanwhile,the expression of TRβ1 protein in male mice sig-nificantly decreased in 0.4 mg/L group(P＜0.01),and the expression of cyclin D1 in each group significantly increased(P＜0.01).The mRNA expression results were basically the same as those of protein expression.After As2 O3 treatment for 194 days,compared with the control group,the expression of TRβ1 protein in each group significantly decreased(P＜0.01),and the expression of cyclin D1 significantly increased(P＜0.01).The mRNA expression results were basically consist-ent with the protein.As2 O3 interfered with the expression of Bcl-2 and Bax proteins in rats and in-duced the increase in the ratio of Bcl-2/Bax protein as the action time increased.Among them,the Bcl-2/Bax ratio of female rats in each group and male rats in the 0.4 mg/L group significantly in-creased(P＜0.01),and male rats in the 0.1 mg/L group significantly increased(P＜0.05).It shows that As2O3 can cause abnormal levels of TRβ1,cyclin D1 and the Bcl-2/Bax ratio in rat liv-er.
关键词
As2O3/肝毒性/甲状腺激素信号通路/甲状腺激素受体β1/大鼠Key words
As2O3/hepatotoxicity/TH signal pathway/TRβ1/rat引用本文复制引用
基金项目
河南省科技发展计划(222102110211)
河南省教育厅重点研发项目(21B230007)
河南省自然科学基金(232300420029)
出版年
2024
NETL
NSTL
万方数据